Cultured human hepatocytes are a well-established in vitro model system for studying drug metabolism and potential toxicity. Routine application of hepatocytes in metabolic stability screening of new chemical entities has led to a variety of low clearance compounds (LCC) for further drug development. These LCCs have the advantages of a favorable pharmacokinetic profile which may have more prolonged pharmacological activity in the human body. Furthermore, these LLCs may be less likely to cause drug-drug interactions.
The cell culture medium must support hepatic functionality in order to reliably predict in vivo response to various drugs. However, some functions of the cultured hepatocytes decrease by more than 50% during the first 24 hours in culture.
Short-term incubations with hepatocytes may not be effective for certain LCCs. For example, the half-life of diazepam is approximately 43±13 hours.
Thus, maintenance of hepatocyte functions in vitro for greater than 24 hours remains a challenging task. Therefore, improvements in hepatocyte culture conditions could be beneficial to the drug discovery process.